In the first three-year period we completed the primry structure determination of prothrombin (including thrombin). During the present three-year period we have determined the complete primary structure of plasminogen. That of antithrombin-III is very close to completion. The A-fragment (fragment-1, containing residues 1-156) from prothrombin, and the elastase-fragment K4 (residues 354-439) from plasminogen have been crystallized. In both cases the crystals are sufficiently well-ordered for high-resolution x-ray crystallography. Each fragment contains a "kringle" structure. The prothrombin fragment has similar Ca2 ion-phospholipid-binding properties to prothrombin and contains the vitamin K-dependent structure. It has been crystallized in the presence of Ca2 ion. The plasminogen fragment K4 contains one of the lysine-binding sites from plasminogn. Fragments of alpha2-macroglobulin (CNBr-fragments) containing about 30 percent of the structures have been completely sequenced. The present project proposes to determine the entire primary structure of alpha2-macroglobulin (which is a general inhibitor of proteolytic enzymes, not only those involved in blood coagulation and fibronolysis) and identify its inhibitor site/area; to study the structural interaction of thrombin and antithrombin-III; to solve the tertiary structures of the crystalline prothrombin and plasminogen fragments.